AR079448A1 - Inhibidores de la esfingosina quinasa - Google Patents

Inhibidores de la esfingosina quinasa

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Publication number
AR079448A1
AR079448A1 ARP100104609A ARP100104609A AR079448A1 AR 079448 A1 AR079448 A1 AR 079448A1 AR P100104609 A ARP100104609 A AR P100104609A AR P100104609 A ARP100104609 A AR P100104609A AR 079448 A1 AR079448 A1 AR 079448A1
Authority
AR
Argentina
Prior art keywords
atoms
het
coz
replaced
mono
Prior art date
Application number
ARP100104609A
Other languages
English (en)
Inventor
Frank Stieber
Dirk Wienke
Original Assignee
Merck Patent Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck Patent Gmbh filed Critical Merck Patent Gmbh
Publication of AR079448A1 publication Critical patent/AR079448A1/es

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    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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Abstract

Para su aplicacion en el tratamiento de enfermedades influenciadas por la inhibicion de la sph-quinasa 1 como enfermedad hiperproliferativa, inflamatoria, angiogena. Reivindicacion 1: Compuestos acordes a la formula (1) en donde significan, respectivamente, independientemente entre sí: R1, R2, R3, R4, R5, R6 R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17 H, D (deuterio), A, OR18, CN, F, CI y NR18R18'; en donde R1 y R2, R3 y R4, R5 y R6, R10 y R11, R12 y R13, R14 y R15, R16 y R17 también pueden formar juntos, respectivamente, =O (oxígeno carbonilo); en donde R9 y R1, R1 y R2, R2 y R3, R3 y R4, R4 y R5, R5 y R6, R6 y R7, R7 y R8, R10 y R11, R11 y R12, R12 y R13, R14 y R15, R15 y R16, R16 y R17 también pueden formar juntos, respectivamente, alquilo cíclico con 3, 4, 5, 6 o 7 átomos de C o Het, con 3, 4, 5, 6 o 7 átomos anulares; en donde R10 y R19, si Y1 = CR19, R11 y R12, R13 y R19, si Y2 = CR19, R14 y R19, si Y1 = CR19, R15 y R16, R17 y R19, si Y2 = CR19 también pueden formar un doble enlace C=C, respectivamente juntos, con un enlace simple y los átomos de C a los que están unidos; R18, R18' H, D o A; R19, R19' H, D, A, OR18, NR18R18', F, CI, Br, CN o Het; M1, M2, M3, M4 CR19 o N; Y1, Y2 CR19 o N; V C(R19)(R19'), NR19 o faltante; W [C(R19)(R19')]pZ, CO-[C(R19)(R19')]pZ, [C(R19)(R19')]pN(R19)-Z, CO-N(R19)- [C(R19)(R19')]pZ, N(R19)-CO-[C(R19)(R19')]pZ, CO-O-[C(R19)(R19')]pZ, C(O)OR18, OR18, H o D; en donde V, W y Y2 también son, respectivamente juntos, alquilo cíclico con 3, 4, 5, 6 o 7 átomos de C, en donde, preferentemente, 1, 2, 3, 4, 5, 6 o 7 átomos de H pueden estar reemplazados por F, CI, Br, CN y/o OH, OR19, OC(O)R19, NR19C(O)OZ, C(O)OR19, C(O)N(R19)(R19') o N(R19)(R19'), o pueden formar Het con 3, 4, 5, 6 o 7 átomos anulares, en donde Het es, preferentemente, un heterociclo saturado, insaturado o aromático con 1 a 4 átomos de N, O y/o S, que puede estar insustituido o mono, bi o trisustitutido por Hal, F, CI, Br, CN, A, OR18, W, SR18, NO2, N(R19)(R19'), NR18COOZ, OCONHZ, NR18SO2Z, SO2N(R18)Z, S(O)mZ, COZ, CHO, COZ, =S, =NH, =NA, Oxy (-O-) y/o =O (oxígeno carbonilo); Z Het, Ar o A; A alquilo no ramificado o de cadena ramificada con 1, 2, 3, 4, 5, 6, 7, 8, 9 o 10 átomos de C, en donde 1, 2, 3, 4, 5, 6 o 7 átomos de H pueden estar reemplazados por F, CI, Br, CN y/o OH, OR19, OC(O)R19, NR19C(O)OZ, C(O)OR19, C(O)N(R19)(R19') o N(R19)(R19'); y/o en donde uno o dos grupos de CH2 pueden estar reemplazados por O, S, SO, SO2, CO, COO, NR18, NR18CO, CONR18, alquilo cíclico con 3, 4, 5, 6 o 7 átomos de C, CH=CH y/o grupos CH:::CH; o alquilo cíclico 3, 4, 5, 6 o 7 átomos de C, en donde, preferentemente 1, 2, 3, 4, 5, 6 o 7 átomos de H pueden estar reemplazados por F, CI, Br, CN y/o OH, OR19, OC(O)R19, NR19C(O)OZ, C(O)OR19, C(O)N(R19)(R19') o N(R19)(R19'); Ar fenilo, naftilo o bifenilo mono, bi o trisustituido por Hal, F, CI, Br, CN, A, OR18, W, SR18, NO2, N(R19)(R19'), NR18COOZ, OCONHZ, NR18SO2Z, SO2N(R18)Z, S(O)mZ, COZ, CHO, COZ, Het respectivamente, e independientemente entre sí, un heterociclo mono, bi o trinuclear, saturado, insaturado o aromático, con 1 a 4 átomos de N, O, y/o S, que puede ser insustituido o mono, bi o trisustituido por Hal, F, CI, Br, CN, A, OR18, W, SR18, NO2, N(R19)(R19'), NR18COOZ, OCONHZ, NR18SO2Z, SO2N(R18)Z, S(O)mZ, COZ, CHO, COZ, =S, =NH, =NA, Oxy (-O-) y/o =O (oxígeno carbonilo), m 1, 2 o 3, n, o 0, 1 o 2, p 0, 1, 2, 3 o 4, con la indicacion de que se excluyen los compuestos de la formula (1), en donde (a) V está ausente, y (b) W = C(O)CH2-Het; así como sus sales, derivados, profármacos, solvatos, tautomeros y estereoisomeros de uso farmacéutico inocuo, inclusive sus mezclas en todas las proporciones.
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